title: Pharmacological efficacy of anti-IL-1β scFv, Fab and full-length antibodies in treatment of rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that mainly causes the synovial joint inflammation and cartilage destruction. Interleukin-1β (IL-1β) is an important proinflammatory cytokine involved in the pathogenesis of RA. In this study, we constructed and expressed anti-IL-1β-full-length antibody in CHO-K1-SV, anti-IL-1β-Fab and anti-IL-1β-scFv in Rosetta. We compared the therapeutic efficacy of three anti-IL-1β antibodies for CIA mice. Mice with CIA were subcutaneously injected with humanized anti-IL-1β-scFv, anti-IL-1β-Fab or anti-IL-1β-full-length antibody. The effects of treatment were determined by arthritis severity score, autoreactive humoral, cellular immune responses, histological lesion and cytokines production. Compared with anti-IL-1β-scFv treatments, anti-IL-1β-Fab and anti-IL-1β-full-length antibody therapy resulted in more significant effect in alleviating the severity of arthritis by preventing bone damage and cartilage destruction, reducing humoral and cellular immune responses, and down-regulating the expression of IL-1β, IL-6, IL-2, IFN-γ, TNF-α and MMP-3 in inflammatory tissue. The therapeutic effects of anti-IL-1β-Fab and anti-IL-1β-full-length antibodies on CIA mice had no significant difference. However, production of anti-IL-1β-full-length antibody in eukaryotic system is, in general, time-consuming and more expensive than that of anti-IL-1β-Fab in prokaryotic systems. In conclusion, as a small molecule antibody, anti-IL-1β-Fab is an ideal candidate for RA therapy.
authors.affiliation: Northeast Agricultural University, School of Life Science, No. 59 Mucai Street, Xiangfang District, 150030 Harbin, Heilongjiang, China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Qi
authors.forename: Xianlong
authors.initials: X
authors.lastname: Ye
authors.forename: Guiping
authors.initials: G
authors.lastname: Ren
authors.forename: Fangming
authors.initials: F
authors.lastname: Kan
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mo
authors.initials: M
authors.lastname: Guo
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Deshan
authors.initials: D
authors.lastname: Li
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D051379:Mice; D057127:Single-Chain Antibodies / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000888:Antibodies, Anti-Idiotypic; D007140:Immunoglobulin Fab Fragments; D053583:Interleukin-1beta; D007376:Interleukin-2; D015850:Interleukin-6; D057127:Single-Chain Antibodies; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse
keywords: Fab; Full-length antibody; Interleukin-1β (IL-1β); Rheumatoid arthritis (RA); Single-chain Fv (scFv)